Immune Modulation of Autoimmunity by Herbal Products

描述（由申请人提供）：根据 5 年前的调查（2002 年全国健康访谈调查，CDC），每年至少有 36% 的美国成年人采用某种形式的补充和替代医学 (CAM) 疗法来满足他们的医疗保健需求。在 CAM 模式中，使用天然植物产品作为有效的治疗实体，以及与传统药物相比草药相对缺乏毒性，使得植物配方的消费在西方世界得到普及。尽管药草被广泛使用，但大多数药草的作用机制仍不清楚。我们使用自身免疫实验模型进行的初步研究表明，中药藤蔓可以抑制临床疾病，并诱导抗原特异性免疫反应的显着变化（例如，细胞因子反应从促炎型转向抗炎型，以及抗原特异性抗体的产生增加）。在这项研究中，我们提出了实验来测试南蛇藤诱导的免疫调节通过 CD4 CD25 T 调节细胞 (Treg)、体内淋巴细胞运输到靶器官、保护性抗体和炎症介质的深入机制。在这方面，我们的提案与 RFA-AT-08-003 的目标非常匹配。目的 1. 研究 CD4 CD25 T 细胞的抑制功能，从而下调南蛇藤喂养大鼠的疾病进程。目标 2. 研究南蛇藤减少潜在致病性 T 细胞迁移至靶器官的机制。目标 3. 确定增强的抗体对疾病相关抗原的反应如何导致自身免疫反应的抑制。目标 4. 测试南蛇藤诱导的靶组织炎症介质调节。尽管这一提议涉及一种 CAM 模式（一种中草药）和一种自身免疫实验模型，但我们相信，我们研究中阐明的基本机制原理也部分适用于其他 CAM 模式以及其他自身免疫模型。 公共健康相关性：天然植物产品越来越多地被患有多种自身免疫性疾病的患者使用，例如糖尿病、多发性硬化症、关节炎和狼疮。然而，许多这些产品的作用机制尚未确定。我们建议研究中草药南蛇藤介导其对抗自身免疫的有益作用的免疫系统相关机制。我们将在自身免疫实验模型中进行这些研究。我们的研究结果将有助于使用植物产品开发合理设计的自身免疫治疗方法。

DESCRIPTION (provided by applicant): At least 36 percent of adult Americans adopted some form of complementary and alternative medicine (CAM) therapy for their healthcare needs annually as surveyed 5 years ago (National Interview Health Survey of 2002, CDC). Among CAM modalities, the use of naturally grown plant products as efficacious therapeutic entities as well as the relative lack of toxicity of herbs compared to conventionally used drugs has popularized the consumption of botanical formulas in the western world. Despite the extensive use of medicinal herbs, the mechanisms of action remain unclear for most of them. Our preliminary study using an experimental model of autoimmunity has revealed that the Chinese herb Celastrus suppresses clinical disease and induces significant changes in antigen-specific immune response (e.g., deviation of the cytokine response from pro-inflammatory to anti-inflammatory type, and increased production of antigenspecific antibodies). In this study, we have proposed experiments to test the in-depth mechanisms of Celastrus-induced immune modulation operative via the CD4+CD25+ T regulatory cells (Treg), the in vivo trafficking of lymphocytes into the target organ, the protective antibodies, and the inflammatory mediators. In this respect, our proposal is an excellent match with the objectives of RFA-AT-08-003. Aim 1. To study the suppressive function of CD4+CD25+T cells that leads to the downregulation of the disease process in Celastrus-fed rats. Aim 2. To examine the mechanisms by which Celastrus reduces the migration of potentially pathogenic T cells into the target organ. Aim 3. To determine how enhanced antibody response to the disease-related antigen leads to suppression of the autoimmune response. Aim 4. To test for the Celastrus-induced modulation of inflammatory mediators in the target tissue. Although this proposal involves one CAM modality (a Chinese herb) and one experimental model of autoimmunity, we believe that the basic mechanistic principles elucidated in our study would also be applicable in part to other CAM modalities as well as other models of autoimmunity. Public Health Relevance: Natural plant products are increasingly being used by patients with a variety of autoimmune diseases, such as diabetes, multiple sclerosis, arthritis and lupus. However, the mechanisms of action of many of these products are not defined. We propose to study the immune system related mechanisms by which Celastrus, a Chinese herb, mediates its beneficial effects against autoimmunity. We will conduct these studies in an experimental model of autoimmunity. The results of our study would help developing rationally designed therapeutic approaches for autoimmunity using botanical products.